title: Serotonin signalling in the gut--functions, dysfunctions and therapeutic targets.
abstract: Serotonin (5-HT) has been recognized for decades as an important signalling molecule in the gut, but it is still revealing its secrets. Novel gastrointestinal functions of 5-HT continue to be discovered, as well as distant actions of gut-derived 5-HT, and we are learning how 5-HT signalling is altered in gastrointestinal disorders. Conventional functions of 5-HT involving intrinsic reflexes include stimulation of propulsive and segmentation motility patterns, epithelial secretion and vasodilation. Activation of extrinsic vagal and spinal afferent fibres results in slowed gastric emptying, pancreatic secretion, satiation, pain and discomfort, as well as nausea and vomiting. Within the gut, 5-HT also exerts nonconventional actions such as promoting inflammation and serving as a trophic factor to promote the development and maintenance of neurons and interstitial cells of Cajal. Platelet 5-HT, originating in the gut, promotes haemostasis, influences bone development and serves many other functions. 5-HT3 receptor antagonists and 5-HT4 receptor agonists have been used to treat functional disorders with diarrhoea or constipation, respectively, and the synthetic enzyme tryptophan hydroxylase has also been targeted. Emerging evidence suggests that exploiting epithelial targets with nonabsorbable serotonergic agents could provide safe and effective therapies. We provide an overview of these serotonergic actions and treatment strategies.
authors.affiliation: Department of Neurological Sciences, D403A Given Building, 89 Beaumont Avenue, University of Vermont, Burlington, VT 05405, USA. gary.mawe@uvm.edu
authors.forename: Gary M
authors.initials: GM
authors.lastname: Mawe
authors.forename: Jill M
authors.initials: JM
authors.lastname: Hoffman
mesh_terms: D017615:Enteric Nervous System / Q000502:physiology*; D005767:Gastrointestinal Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D005769:Gastrointestinal Motility / Q000502:physiology; D041981:Gastrointestinal Tract / Q000294:innervation / Q000502:physiology; D006801:Humans; D012701:Serotonin / Q000502:physiology*; D018490:Serotonin Agents / Q000627:therapeutic use*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D018490:Serotonin Agents; D012701:Serotonin